Are current guidelines on caffeine use in sport optimal for everyone? That's the question two sports nutritionists pose as they argue that genetic variation may well influence caffeine's performance-enhancing effects.

The theory stems from the substantial variation seen between individuals and improvements in performance following caffeine ingestion in sport.

These differences, say the researchers, are partly mediated by genetic variation between individuals.

Knowledge of this variation could lead to the development of improved caffeine usage guidelines for not only professional athletes but members of the public looking to keep fit and improve their health.

“I think the key message is that, despite the generalised guidelines, amateur athletes and even general consumers should experiment with different amounts of caffeine to see what works best for them,”​ said Craig Pickering, study co-author and head of sport science at genetic testing company DNAFit.

“There is no one-size fits-all caffeine advice, and so we should stop pretending there is.”​

CYP1A2 and ADORA2A​

Pickering believes a personalised caffeine intake can be garnered by focusing on the differences in nucleotide sequence (polymorphisms) within two genes, CYP1A2 and ADORA2A.

Here, Pickering along with study co-author John Kiely, are adamant that genetic factors exert a large influence on individual responses to caffeine ingestion, even if these factors and their mechanisms have so far not been completely clarified.

“Regarding CYP1A2, it is speculated it could be due to a more rapid accumulation of caffeine metabolites in AA genotypes, which are hypothesised to potentially have a greater ergogenic effect than caffeine itself,”​ the authors comment.

“If correct, then caffeine timing becomes important; it might not be that C allele carriers find caffeine less ergogenic, just that it requires longer for caffeine to be metabolised to its ergogenic metabolites.” ​

Nature vs. nurture​

Both authors acknowledge though the complexity of what they are proposing and recognise that caffeine’s effects do not solely depend on genetic make-up of an individual.

Other non-genetic, but controllable, factors include its dose, source, age, timing, time of day and training status.

“Caffeine's is, without a doubt, affected by these factors,”​ said Pickering. “How recently you consumed a meal, for example, could alter gastric emptying, and hence caffeine absorption; if you’re taking caffeine to enhance performance, you want it in your bloodstream as soon as possible, so taking it with a large meal may be negative. ​

“Similarly, consuming large amounts of cruciferous vegetables on a regular basis may increase the speed at which caffeine is metabolised, which may be good or bad - we’re not sure yet.” ​

Pickering adds that he sees no reason why these principles can’t be applied to other nutrients used in enhancing sporting performance.

Previous research confirms certain individuals absorb nutrients from their digestive system at a greater rate, influencing how much and when they need to consume those nutrients.

In addition, some people will likely be predisposed to store increased amounts of creatine for example in their muscles, which will impact supplementation practice.

This is most clear around vitamin requirements; certain individuals have gene variants which mean they require more of a nutrient. These differences can be a guide to personalise nutrition.

Conclusions: What next?​

In the long-term, developments in genetic profiling technology give rise to possibilities these insights may soon be readily available to sporting populations.

Naturally, the sports supplement industry would look to capitalise on such information with the idea that nutrient and vitamin supplies specifically tailored to requirements cannot be a concept too far off in the future.

“I think a move towards more personalised supplement recommendations will happen,”​ he said “although there are still a lot of aspects we need to better understand before this is possible- but we’re getting there!”​

As the study concludes current generalised guidelines of 3–9 milligrams per kilogram (mg/kg), 60 min prior are clearly not optimal for everyone.

But what is not clear, however, is what these guidelines should be. Simply put, too many questions remain.

Can other genes that modify caffeine ergogenicity be identified? Are there different optimal dosages and timing strategies for different genotypes? And does caffeine habituation occur differently across genotypes?

Only by answering these questions can athletes be able to fully maximise the performance enhancing effects of caffeine in a way that is matched to their unique biology.

Being able to develop more precise, individualised guidelines would be beneficial, especially given the prevalent use of caffeine in elite sports.

Source: Sports Medicine​Published online ahead of print: doi.org/10.1007/s40279-017-0776-1​​“Are the Current Guidelines on Caffeine Use in Sport Optimal for Everyone? Inter-individual Variation in Caffeine Ergogenicity, and a Move Towards Personalised Sports Nutrition.”​Authors: Craig Pickering, John Kiely